Chapter 18 –Metabolic Liver Disease-NAFLD

Question 1

Metabolic Liver Disease

A distinct group of liver diseases is attributable to disorders of metabolism, either acquired or
inherited.

What is the most common acquired metabolic disorder?

Answer 1

non-alcoholic fatty liver disease

Question 2

What are the most prominent among among inherited metabolic diseases?

Answer 2

• hemochromatosis,
• Wilson disease, and
• α1-antitrypsin.

Question 3

What is a broad disease category encompassing rare inherited diseases and neonatal

infections

Answer 3

Also included among liver metabolic diseases is neonatal

hepatitis, a broad disease category encompassing rare inherited diseases and neonatal

infections

Question 4

Metabolic Liver Disease

Answer 4

• NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)
• HEMOCHROMATOSIS
• WILSON DISEASE
• α1-ANTITRYPSIN DEFICIENCY
• NEONATAL CHOLESTASIS

Question 5

What is NAFLD?

Answer 5

is a group of conditions that have in common the presence of hepatic steatosis (fatty
liver),in individualswho do not consume alcohol, or do so in very small quantities (less than 20
g of ethanol/week).

Question 6

What has become the most common cause of chronic liver disease in theUnited States, and in its various forms, probably affects more than 30% of the population?

Answer 6

NAFLD

However, these estimates are approximate, because fatty liver without other complications may
not be detected clinically.

Question 7

NAFLD includes what?

Answer 7

• simple hepatic steatosis,
• steatosis accompanied by minor, non-specific inflammation, and
• non-alcoholic steatohepatitis (NASH). [43]

Question 8

What is Steatosis with or without non-specific inflammation?

Answer 8

is generally a stable condition without significant clinical problems.

Question 9

What is NASH?

Answer 9

NASH is a condition in which there is hepatocyte injury that may progress to cirrhosis in 10% to 20% of cases.

Question 10

What are the main components of NASH?

Answer 10

• hepatocyte ballooning,
• lobular inflammation, and
• steatosis. [44]

NOTE: With progressive disease fibrosis occurs

Question 11

What gender is mostly affected by NASH?

.

Answer 11

affects men and women equally

Question 12

What condtition is strongly associated with NASH?

Answer 12

• with obesity and the o
• ther components of the metabolic syndrome, such as
  
  • dyslipidemia,
  • hyperinsulinemia and
  • insulin resistance.

Question 13

What is the epidemiology of NAFLD?

Answer 13

It is estimated that more than 70% of obese individuals have some form of NAFLD.

Question 14

What is the most common cause of so-called cryptogenic cirrhosis, namely cirrhosis of “unknown”origin?

Answer 14

NAFLD

contributes to the progression of other liver diseases such as HCV infection and

HCC. The epidemic of obesity in the United States heightens concern that NAFLD will increase

in prevalence.

Question 15

What is the pathogenesis of NAFLD?

Answer 15

The precise mechanisms of steatosis and hepatocellular damage in NAFLD are not entirely
known, but genetics and environment play a role in the pathogenesis. [44]

A “two-hit” model of
pathogenesis has been proposed, encompassing two sequential events:

(1) hepatic fat accumulation and,

(2) hepatic oxidative stress.

The oxidative stress acts upon the
accumulated hepatic lipids, resulting in lipid peroxidation and the release of lipid peroxides,
which can produce reactive oxygen species.

Question 16

What are the clinical features of NAFLD?

Answer 16

Individuals with simple steatosis are generally asymptomatic.

Clinical presentation is often related to other metabolic derangements, such as obesity, insulin resistance, and diabetes. [46]

Question 17

What is revealed in the imaging studies of NAFLD?

Answer 17

Imaging studies may reveal fat accumulation in the liver.

Question 18

What is the most
reliable diagnostic tool for NASH and helps determine the extent of steatosis, presence of
steatohepatitis, and degree of fibrosis?

Answer 18

liver biopsy

Question 19

What is the laboratory picture of NASH?

Answer 19

Serum AST and ALT are elevated in about 90% of
patients with NASH.

Question 20

What is the lab picture of alcoholic steatohepatitis?

Answer 20

The AST/ALT ratio is usually less than 1, in contrast to alcoholic steatohepatitis in which the ratio is generally above 2.0 to 2.5.

Question 21

Despite the enzyme elevations,
patients may be asymptomatic. Others have general symptoms such as fatigue and right-sided
abdominal discomfort caused by hepatomegaly.

Why is cardiovascular disease a frequent cause of death in NASH?

Answer 21

Because of the association between NASH and
the metabolic syndrome, cardiovascular disease is a frequent cause of death in patients with
NASH.

Question 22

What is the goal of treating individuals with NASH?

Answer 22

is to reverse the steatosis and prevent
cirrhosis.

The current management strategy seeks to correct the underlying risk factors, such as obesity and hyperlipidemia, and to treat insulin resistance

Question 23

What are the risk factors for NASH?

Answer 23

• such as obesity and
• hyperlipidemia, and to
• treat insulin resistance

Question 24

What is the morphology of steatosis?

Answer 24

Steatosis usually involves more than 5% of the hepatocytes and sometimes
more than 90%.

Large (macrovesicular) and small (microvesicular) droplets of fat, predominantly triglycerides, accumulate within hepatocytes ( Fig. 18-25A ).

At the most clinically benign end of the spectrum, there is no appreciable hepatic inflammation,
hepatocyte death, or scarring, despite persistent elevation of serum liver enzymes.

Question 25

What is the characteristic of Steatohepatitis (NASH)?

Answer 25

is characterized by steatosis and multifocal parenchyma inflammation, mainly neutrophils, Mallory bodies, hepatocyte death (both ballooning
degeneration and apoptosis), and sinusoidal fibrosis.

Fibrosis also occurs within portal tracts
and around terminal hepatic venules ( Fig. 18-25B ).

These histological changes are similar
to those of alcoholic steatohepatitis.

Cirrhosis may develop, presumably the result of years
of subclinical progression of the necroinflammatory and fibrotic processes.

When cirrhosis is
established, the steatosis or steatohepatitis tends to be reduced and sometimes is not
identifiable.

Question 26

Answer 26

FIGURE 18-25 Histologic appearance of nonalcoholic fatty liver disease.

A, Liver tissue
with macrovesicular steatosis (H&E stain).

B, NASH, showing perivenular fibrosis and
perisinusoidal fibrosis (blue fibers) in this trichrome stain.